Device for drug delivery

ABSTRACT

Disclosed is an ambulatory therapeutic fluid delivery device ( 10 ). The device includes at least one housing ( 200 ) connectable to a cannula ( 250 ), the at least one housing retaining a reservoir ( 220 ) to hold the therapeutic fluid. The device also includes a mechanically powered pumping mechanism ( 150 ) to cause delivery of at least some of the fluid from the reservoir, and a power-transfer mechanism to transfer manually-delivered power provided by a user to mechanically actuate the pumping mechanism.

FIELD OF THE INVENTION

The present disclosure generally relates to a device for medicalinfusion of fluids (e.g., drugs). In particular, the disclosure relatesto a portable infusion device for delivery of an injectable therapeuticfluid. Even more particularly, the disclosure relates to a portable,manually-powered, skin-securable, injectable drug dispensing device.

BACKGROUND OF THE INVENTION External Infusion Pump

An external infusion pump may be medically necessary for theadministration of various medications, intravenously or subcutaneously.Such external infusion devices are used when parenteral administrationof the drug at home is reasonable and/or necessary, when it is requiredthat an infusion pump safely administers the drug, and/or when the drugis administered by a prolonged infusion (e.g., during at least 8 hours)because of proven clinical efficacy.

External infusion pumps (“EIP”) can be used, particularly in anon-hospital setting, to administer antibiotics, chemotherapy,analgesics and opioids, total parenteral nutrition formulas, insulin,vasopressors, blood products, growth hormone, gonadotropin releasinghormone (GnRH), interferon γ, and other drugs or biologics for whichdelivery at a controlled rate of the fluid is desirable or necessary.Functional EIP infusion rates range from high volume delivery rates (400mL/h) for hydration therapy to very low flow rates (0.04 mL/h) that canbe used for delivery chemotherapeutic agents.

Diabetes and Glycemic Control

The term Diabetes mellitus (“DM”) refers to a group of common metabolicdisorders that share the phenotype of hyperglycemia. Several distincttypes of DM exist and are caused by complex interaction of genetics,environmental factors, and life-style. The metabolic dysregulationassociated with all types of DM, especially when glucose levels areuncontrolled, causes secondary pathophysiologic changes in multipleorgan systems that impose a tremendous burden on the individual withdiabetes and on the health care system. In the United States, DM is theleading cause of end-stage renal disease (ESRD), nontraumatic lowerextremity amputations, and adult blindness. With an increasing incidenceworldwide, DM will be a leading cause of morbidity and mortality for theforeseeable future.

The two broad categories of DM are designated type 1 and type 2.Generally speaking, type 1 DM results from autoimmune beta celldestruction, whereas type 2 DM is a heterogeneous group of disorderscharacterized by variable degrees of insulin resistance, impairedinsulin secretion, and increased glucose production.

Type 1 DM

Type 1 DM develops as a result of the synergistic effects of genetic,environmental, and immunologic factors that ultimately destroy thepancreatic beta cells. Individuals with a genetic susceptibility havenormal beta cell mass at birth but begin to lose beta cells secondary toautoimmune destruction that occurs over months to years. As beta cellmass begins to decline, insulin secretion becomes progressivelyimpaired. Features of diabetes generally do not become evident until amajority of beta cells are destroyed (˜80%).

Because individuals with type 1 DM lack endogenous insulin production,administration of basal, exogenous insulin is essential for regulatingglycogen breakdown, gluconeogenesis, lipolysis, and ketogenesis.Likewise, insulin replacement for meals should be appropriate for thecarbohydrate intake and promote normal glucose utilization and storage.A goal of intensive diabetes management is to achieve euglycemia ornear-normal glycemia. This approach requires insulin regimen thatmatches glucose intake and insulin dose. Insulin regimens usuallyinclude multiple-component insulin regimens, multiple daily injections(MDI), or insulin infusion devices (Harrison's principles of internalmedicine, 16th edition, chapter 323).

The benefits of intensive diabetes management and improved glycemiccontrol has been shown in the Diabetes Control and Complications Trial(DCCT) that demonstrated that development and progression of the chroniccomplications of diabetes are greatly related to the degree of alteredglycemia as quantified by determinations of glycohemoglobin (HbA1c).[DCCT Trial, N. Engl. J. Med. 1993; 329: 977-986, UKPDS Trial, Lancet1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N.Engl. J. Med. 2005; 353, (25): 2643-53].

In all MDI regimens, intermediate—or long-acting insulins (e.g., NPH,lente, ultralente, or glargine insulin) supply basal insulin, whereasshort acting insulin (e.g., regular, insulin aspart, or lispro insulin)provides prandial insulin. Lispro and insulin aspart should be injectedjust before or just after a meal; regular insulin dosages are given 30to 45 min prior to a meal. No insulin MDI regimen reproduces the preciseinsulin secretory pattern of the pancreatic islet. However, the mostphysiologic regimens entail more frequent insulin injections, greaterreliance on short-acting insulin, and more frequent capillary plasmaglucose measurements (Harrison's Principles of Internal Medicine, 16thedition, chapter 323).

In recent years, ambulatory portable insulin infusion pumps have emergedas a superior alternative to multiple daily injections of insulin. Thesepumps, which deliver insulin at a continuous or periodic basal rate, aswell as in bolus volumes, were developed to liberate patients fromrepeated self-administered injections, and allow greater flexibility indose administration. The insulin infused via the insulin pump is usuallya short acting insulin (e.g., insulin aspart, lispro insulin).

Currently, about 80% of Type 1 DM patients are managed with MDI, whereasonly about 20% are managed with insulin pumps.

Type 2 DM

Type 2 DM is characterized by impaired insulin secretion, peripheralinsulin resistance, and excessive hepatic glucose production. Obesity,particularly visceral or central is very common in type 2 DM.

Insulin resistance can be defined as a decreased ability of insulin toact effectively on peripheral target tissues (especially muscle andliver). In the early stages of the disorder, glucose tolerance remainsnormal, despite insulin resistance, because the pancreatic beta cellscompensate by increasing insulin output. As insulin resistance andcompensatory hyperinsulinemia progress, the pancreatic islets are unableto sustain the hyperinsulinemic state. Impaired Glucose Tolerance (IGT),characterized by elevations in postprandial glucose, then develops. Afurther decline in insulin secretion and an increase in hepatic glucoseproduction may lead to overt diabetes with fasting hyperglycemia.Ultimately, beta cell failure may ensue.

Increased hepatic glucose production in Type 2 DM may be due to thefailure of hyperinsulinemia to suppress gluconeogenesis in the liver asa result of the insulin resistance. Type 2 DM management can begin withmedical nutritional therapy (“MNT”) and increased physical activity. Ifnot sufficient to achieve glycemic control, pharmacologic therapy isindicated. Pharmacologic approaches to the management of type 2 DMinclude the administration of both oral glucose-lowering agents andinsulin. Usually oral drugs are initiated first.

Several types of oral glucose-lowering agents that target differentpathophysiologic processes in Type 2 DM exist. These include agents thatincrease insulin secretion (e.g., sulfonylurea), reduce glucoseproduction (e.g., metformin), decrease glucose absorption (e.g.,acarbose) and/or increase insulin sensitivity (e.g., pioglitazone).

Insulin Therapy can be considered as the initial therapy in situationsinvolving, for example, lean individuals or individual experiencingsevere weight loss, situations involving individuals with underlyingrenal or hepatic disease that precludes oral glucose-lowering agents, orin situations involving individuals who are hospitalized or acutely ill.Insulin therapy is ultimately required by a substantial number ofindividuals with Type 2 DM because of the progressive nature of thedisorder and the relative insulin deficiency that develops in patientswith long-standing diabetes. (Harrison's Principles of InternalMedicine, 16th edition, chapter 323).

The United Kingdom Prospective Diabetes Study (UKPDS), one of thelargest and longest trial ever conducted in patients with type 2diabetes, found that for each 1% reduction in hemoglobin A1C, there wasa significant decrease in diabetic complications. (BMJ 1995; 310(6972):83-8.). A decline in A1C was best achieved by early exogenous insulintherapy.

Despite the increased risk of mild hypoglycemia, aggressive therapy thatcombines patient education and self-management with a form of exogenousinsulin that closely mimics normal insulin secretion can help to reducethe morbidity and mortality associated with type 2 diabetes. (ClinicalDiabetes 2003; 21:14-21).

Pramlintide Acetate (Symlin)

Amylin is a second β-cell hormone that is co-localized and co-secretedwith insulin in response to meals. Consequently, β-cell dysfunction ininsulin-requiring subjects with type 1 or type 2 diabetes ischaracterized by a markedly impaired postprandial secretory response ofboth insulin and amylin. Amylin acts as a neuroendocrine hormone thatcomplements the effects of insulin in postprandial glucose regulationthrough several centrally mediated effects. These include a suppressionof postprandial glucagon secretion and a vagus-mediated regulation ofgastric emptying, thereby helping to control the influx of endogenousand exogenous glucose, respectively. Amylin has also been shown toreduce food intake and body weight, consistent with an additionalsatiety effect. Consistent with these findings, mealtime amylinreplacement, as an adjunctive therapy to insulin, may improve metaboliccontrol in diabetic subjects.

Pramlintide is a soluble, non-aggregating synthetic peptide analog ofhuman amylin that has a potency at least equal to that of native amylin.Pramlintide in insulin-requiring subjects with diabetes has been shown,as an adjunct to insulin therapy, to correct postprandialhyperglucagonemia, slow the delivery of nutrients from the stomach tothe small intestine, and, concomitantly, improve postprandial glucoseexcursions. (Diab. Tech. Therp. 2002; 4(1):51-61.). Pramlintide isinjected subcutaneously with a standard insulin syringe, rendering thedosage flexible.

Exentide

Incretins are gut-derived factors that increase glucose stimulatedinsulin secretion. Exentide (byetta) is an incretin mimetic thatincreases insulin secretion, increase beta cell growth/replication,slows gastric emptying, and may decrease food intake. Exentide isindicated as an adjunctive therapy to improve glycemic control in type 2diabetic patients who are taking one or more of the following oralanti-diabetic drugs: Metformin, sulfonylurea, thiazolidinedione.Exentide is administered before a meal as a subcutaneous injection.

Insulin Pumps

Currently available insulin pumps, developed mainly for type 1 DMpatients, deliver rapid acting insulin 24 hours-a-day through a catheterplaced under the skin (i.e., subcutaneously). The total daily insulindose can be divided into basal and bolus doses.

Basal insulin is delivered continuously over 24 hours, and keeps theblood glucose concentration levels (in brief blood glucose levels) innormal desirable range between meals and overnight. Basal insulindelivery rate can be changed during the day to counteract changingdiurnal insulin requirements, for example during physical activity,sleeping, etc. Moreover, a specific daily basal administration curve canbe stored (designated as a “basal profile”) and retrieved upon patientdiscretion.

Insulin bolus doses are delivered before or after meals to counteractcarbohydrates loads or during episodes of high blood glucoseconcentration levels. Current pumps contain electronic components andare provided with the necessary software to precisely calculate bolusdoses according to meal size and carbohydrate content.

Due to the fact that Type 2 DM patients usually have some residualendogenous insulin, the basal/bolus administration mode of currentlyexisting pumps is unnecessary, for the following reasons:

-   -   1. Most patients have enough insulin to sustain the basal        requirements of the body but not to counteract the carbohydrates        consumed in meals.    -   2. Basal requirements are usually met by a single long acting        insulin injection per day (i.e., Glargine, Detemir).    -   3. Precise bolus dosing is of no clinical relevance because the        amount of residual endogenous insulin and insulin resistance are        unknown.    -   4. Conventional insulin pumps are costly, particularly because        they include relatively expensive electronic components which        are mainly used to control basal administration.

For these reasons, DM type 2 patients tend not to use insulin pumps.

Under some circumstances, conventional insulin pumps, although developedprimarily for Type 1 DM patients, may not be appropriate for all Type 1DM patients, for the following reasons:

-   -   1. The underlying technology involved makes currently available        pumps relatively expensive and therefore not adequate for low        budget patients.    -   2. The underlying technological sophistication of currently        available pumps require learning of the many installed features,        an endeavor that makes many individuals uncomfortable with the        use of these devices (i.e., fear of technology).    -   3. A major drawback of currently available pumps is their large        size and weight, caused in part by numerous electronic        components and the relatively large driving mechanism of these        devices. These uncomfortable bulky fluid delivery devices are        rejected by many diabetic insulin users.

SUMMARY OF THE INVENTION

Disclosed herein is a dispensing device which obviates the problems ofconventional infusion devices and provides an improved device which iseasy to use, affordable and operationally intuitive for diabeticpatients.

In some embodiments, a portable device for bolus(es) delivery ofinjectable therapeutic fluid into the body of the patient at thepatient's discretion is provided.

In some embodiments, a device for delivery of one or more anti-diabeticinjectable drug bolus(es) to the body to achieve better glycemic controlis described.

In some embodiments, a device that is miniature, discreet,user-friendly, economical for users and cost-effective for the payerthat can deliver injectable drugs into the body of the patient isprovided. The device can be configured to include a durable reusablepart that contains the relatively expensive component(s) (e.g., adriving mechanism), and a disposable part to house the relativelycheaper components (e.g., a reservoir).

In some embodiments, a device that includes a miniature patch unit thatcan be secured to the skin and can deliver injectable drugs (e.g., inbolus doses) into the body is described. In some embodiments, bolusdose(s) adjustments and/or administrations can be done manually. In someembodiments, such adjustments and/or administrations can be doneautomatically and/or periodically, or be based on any desired schedule(e.g., scheduling profiles stored in a storage device that can beaccessed by a controller and/or the user). In some embodiments, a devicethat can be easily connected and disconnected from a subcutaneouscannula is provided.

In some embodiments, the dispensing device includes two parts: adisposable part and a reusable part. The disposable part includes areservoir intended to be filled with some therapeutic fluid (e.g.,insulin) and an outlet port through which the fluid is transferred tothe patient's body. The reusable part includes a driving mechanismand/or a pumping mechanism. The dispensing device may be operable uponconnection of the two parts.

In some embodiments, neither the disposable part nor the reusable partincludes electronic to enable low production cost and, as a result, afinancially affordable device for DM patients. Such devices may includea manually-power pumping mechanism and a power transfer mechanism totransfer manually-generated power provided by a user.

In some embodiments, the pumping mechanism may be a peristaltic-typemechanism, a piston-based mechanism, etc.

In some embodiments, the device is manually operable (e.g.,manually-powered) and the power transfer mechanism (also referred to asa driving mechanism) includes mechanical components (e.g., springs,gears, etc.) and is implemented without components requiringelectrically-generated power and/or without any electronic components(e.g., CPU, electronically-controlled sensors).

In some embodiments, operation of the device is relatively easy andsimple, and includes, for example, pressing (actuating) of buttons or ofa blower. Operating the disclosed device does not require anyspecialized skills, technical support and/or training, thus enablingoperation of such device by patients who are less adept technologically,or who are otherwise apprehensive about dealing with complicatedsoftware or electronic device and/or applications.

Further embodiments described herein include a controller to monitor theamount of the dispensed therapeutic fluid and the fluid remaining in thereservoir. In some embodiments, an indicator, such as, for example, adetachable digital counter, enables the display of operationalparameters (e.g., number of units delivered). In some embodiments, theindicator is cost-effective and requires a simple electric circuit.

In some embodiments, the reservoir holding the therapeutic fluid andhoused within the device may be configured in various sizes to holddifferent volumes of therapeutic fluid.

In some embodiments, the reservoir holding the therapeutic fluid andhoused within the device may be configured to hold different types oftherapeutic fluid to enable delivery of various therapeutic fluids atthe patient's discretion.

In one aspect, an ambulatory therapeutic fluid delivery device isdisclosed. The device includes at least one housing connectable to acannula, the at least one housing retaining a reservoir to hold thetherapeutic fluid. The device also includes a mechanically poweredpumping mechanism to cause delivery of at least some of the fluid fromthe reservoir, and a power-transfer mechanism to transfermanually-delivered power provided by a user to mechanically actuate thepumping mechanism.

Embodiments of the device may include one or more of the followingfeatures.

The device may further include a subcutaneously insertable cannula influid communication with the reservoir.

The device may be skin adherable.

The reservoir may be fellable by the user.

The mechanically-powered pumping mechanism may be configured to operatewithout using electrically-generated power.

The therapeutic fluid may includes one or more of, for example, insulin,Pramlintide acetate and/or Exentide (also referred as Exenatide, whichis commercially known as BYETTA™).

The at least one housing may include a disposable part housing includingat least a part of the reservoir and an outlet port to enable passage ofthe fluid to a body of the patient, and a reusable part housingattachable to the disposable part, the reusable part housing includingat least the pumping mechanism and the power-transfer mechanism. Thereservoir may be configured to be filled with the fluid prior toattachment of the disposable part to the reusable part.

The power-transfer mechanism may include a user-actuated rotateablewheel, and one or more gears coupled to the rotateable wheel and furthercoupled to the mechanically-powered pumping mechanism, the one or moregears configured to actuate the pumping mechanism to cause the deliveryof the at least some of the fluid in response to rotation of theuser-actuated wheel. The one or more gears may include at least one cogwheel in mechanical communication with at least one worm gear, and ascrew-nut coupled to the worm gear and further coupled to a piston suchthat rotation of the screw nut causes displacement of the piston.

The mechanically-powered pumping mechanism may include a piston coupledto the reservoir, the piston further coupled to the power-transfermechanism. Actuation of the piston by the power-transfer mechanism maycause displacement of the piston such that the piston causes at leastsome of the fluid in the reservoir to be displaced.

The device may further include a handle coupled to the piston to enablemanual displacement of the piston. The device may further include alimiter to prevent displacement of the piston beyond a pre-set spatialposition defined by the limiter. The limiter may include a stationaryblock to engage a projection extending from an end of the piston suchthat upon contact between the stationary block and the projectionextending from the end of the piston, further displacement of the pistonis prevented.

The pumping mechanism may include a peristaltic-type pumping mechanism.The peristaltic-type pumping mechanism may include a rotor coupled to adelivery tube to deliver therapeutic fluid, the rotor further coupled tothe power-transfer mechanism such that manual power transferred by thepower-transfer mechanism causes rotation of the rotor to causedisplacement of therapeutic fluid contained within the delivery tube.

The power-transfer mechanism may include a spring-based mechanismactuated by the user, the spring-based mechanism configured to actuatethe pumping mechanism upon actuation of the spring-based mechanism bythe user. The spring-based mechanism may include a spiral spring coupledto at least one gear, the spiral spring biased in a first rotationaldirection, and a string coupled to the spiral spring to cause rotationof the spiral spring in another rotational direction to cause anincrease in the tension of the spiral spring. Upon release of thestring, the spiral spring may rotate in the first rotational directionto cause actuation of the power-transfer mechanism coupled to the spiralspring. The string may be configured to be moved to a position such thatupon release of the string the spiral spring rotates a pre-definedradial distance that causes actuation of the pumping mechanism by anamount corresponding to delivery of a pre-determined amount oftherapeutic fluid.

The pumping mechanism may include an inflatable air container to actuatethe reservoir. The power-transfer mechanism may include at least one airinjection device to deliver air to the inflatable air container. The atleast one air injection device may include an air tube in communicationwith the inflatable air container, and an air compression chamber incommunication with the air tube, the air compression chamber including adisplaceable plunger. Upon actuation of the plunger by the user, air maybe displaced from the air compression chamber into the inflatable aircontainer through the air tube.

The device may further include an indicator to indicate operation of themechanically powered pumping mechanism. The indicator may include one ormore of, for example, an audible indicator to produce a sound and/or avisual indicator to produce a visual signal.

The device may further include a counter to display a valuerepresentative of an amount of therapeutic fluid delivered and/or to bedelivered by operation of the device. The counter may be configured toindicate delivery of discrete bolus doses of the fluid from thereservoir. The counter may be configured to display units representativeof the amount of delivered therapeutic fluid, each of the displayed unitrepresentative of a pre-defined amount of the delivered therapeuticfluid. Operation of the counter may be based on operation of thepower-transfer mechanism. Operation of the counter may be based on theoperation of the power-transfer mechanism such that the power transfermechanism actuates the counter. The counter may include a mechanicallydetachable counter housing configured to be attached and detached fromthe at least one housing.

The device may further include a measurement unit to determine extent offluid delivered. The measurement unit may include an optical unit todetect one or more markings disposed on the power-transfer mechanism.The detection of the one or more markings may be indicative that apre-determined amount of fluid was delivered. The power transfermechanism may include a gear having one or more holes extending from onesurface of the gear to the other surface. The optical unit may include alight source to illuminate a light beam towards the one surface of thegear, and a light sensor to detect light passing through the one or moreholes.

The device may further include a cradle unit configured to receive theat least one housing retaining the reservoir, the cradle unit beingsecurable to skin of a patient. The cradle unit may include an adhesivesurface configured to be adhered to the skin of a patient, at least onelatch configured to secure the at least one housing to the cradle unit,and a well to enable passage of the cannula therethrough. The device mayfurther include a cannula cartridge unit, and the cannula may besubcutaneously insertable from the cannula cartridge unit through thecradle unit.

The device may further include an adapter connectable to the reservoirand further connectable to a refilling vial containing therapeutic fluidto be added to the reservoir.

The at least one housing may be configured to receive different sizereservoirs.

In another aspect, an ambulatory therapeutic fluid delivery device isdisclosed. The device includes at least one housing connectable to acannula, the at least one housing retaining a reservoir to hold thetherapeutic fluid. The device also includes a piston coupled to thereservoir, and a power-transfer mechanism to transfer manually-deliveredpower provided by a user to mechanically actuate the piston. Actuationof the piston by the power-transfer mechanism causes displacement of thepiston such that the piston causes at least some of the fluid in thereservoir to be displaced.

Embodiments of the device may include any of the features of the firstdevice described above.

In a further aspect, an ambulatory therapeutic fluid delivery device isdiscloses. The device includes at least one housing connectable to acannula, the at least one housing retaining a reservoir to hold thetherapeutic fluid. The device also includes a piston coupled to thereservoir, a user-actuated rotateable wheel, and one or more gearspowered by manually-delivered power generated by a user, the one or moregears coupled to the rotateable wheel and further coupled to the piston.In response to rotation of the user-actuated wheel by the user the oneor more gears mechanically actuate the piston to displace the piston andcause delivery of at least some of the fluid.

Embodiments of the device may include any of the features of the devicesdescribed above.

In yet another aspect, an ambulatory therapeutic fluid delivery deviceis disclosed. The device includes a reservoir to hold the therapeuticfluid, a peristaltic-type pumping mechanism, and a power-transfermechanism to transfer manually-delivered power provided by a user tomechanically actuate the peristaltic-type pumping mechanism. Actuationof the peristaltic-type pumping mechanism by the power-transfermechanism causes movement of the peristaltic-type pumping mechanism suchthat the peristaltic-type pumping mechanism causes at least some of thetherapeutic to be displaced.

Embodiments of the device may include any of the features of the devicesdescribed above.

In another aspect, an ambulatory therapeutic fluid delivery device isdisclosed. The device includes a reservoir to hold the therapeuticfluid, a rotor coupled to a delivery tube to deliver some of thetherapeutic fluid, a user-actuated rotateable wheel, and one or moregears powered by manually-delivered power generated by a user, the oneor more gears coupled to the rotateable wheel and further coupled to therotor. In response to rotation of the user-actuated wheel by the userthe one or more gears mechanically actuate the rotor to causedisplacement of fluid contained in the delivery tube.

Embodiments of the device may include any of the features of the devicesdescribed above.

In a further aspect, an ambulatory therapeutic fluid delivery device isdisclosed. The device includes a reservoir to hold the therapeuticfluid, an inflatable air container to actuate the reservoir, and atleast one manually-actuated air injection device to deliver air to theinflatable air container. Inflation of the air container causes at leastsome of the fluid in the reservoir to be displaced.

Embodiments of the device may include any of the features of the devicesdescribed above.

In yet another aspect, a method to administer therapeutic fluid held ina reservoir is disclosed. The method includes transferringmanually-generated power provided by a user to a mechanically-poweredpumping mechanism disposed in at least one housing connectable to acannula, the at least one housing further retaining the reservoir. Themethod further includes mechanically actuating the pumping mechanism tocause delivery of at least some of the therapeutic fluid.

Embodiments of the method may include any of the features of the devicesdescribed above, as well as one or more of the following features.

Actuating the pumping mechanism may include actuating the pumpingmechanism without using electrically-generated power.

Transferring the manually-generated power may include rotating auser-actuated rotateable wheel, and causing actuation of one or moregears coupled to the rotateable wheel in response to rotation of therotateable wheel to cause actuation of the mechanically-powered pumpingmechanism. The one or more gears may include at least one cog wheel inmechanical communication with at least one worm gear, and a screw-nutcoupled to the worm gear and further coupled to a piston such thatrotation of the screw nut causes displacement of the piston.

Actuating the pumping mechanism may include actuating a piston coupledto the reservoir, the piston further coupled to the power-transfermechanism, and displacing the at least some of the fluid in response toactuation of the piston by the power-transfer Mechanism.

The method may further include displaying a value representative of anamount of therapeutic fluid delivered. Displaying the value may includedisplaying a value indicative of delivery of discrete bolus doses of thefluid from the reservoir. Displaying the value may includes displayingthe value representative of an amount of therapeutic fluid deliveredbased on extent of the manually generated power provided by the user.

The method may further include determining extent of fluid delivered.Determining the extent of the fluid delivered may include detecting oneor more markings disposed on a power-transfer mechanism to transfer themanually generated power. The detection of the one or more markings maybe indicative that a pre-determined amount of fluid was delivered.Detecting the one or more markings may include illuminating a light beamtowards a first surface of the power-transfer mechanism having one ormore holes extending from the first surface to another surface of thepower-transfer mechanism, and detecting light passing through the one ormore holes.

More features and embodiments of the present inventions will beillustrated in the detailed description.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 a is a schematic diagram of an exemplary single-part fluiddelivery device.

FIG. 1 b is a schematic diagram of an exemplary two-part fluid deliverydevice.

FIGS. 2 a-c are views illustrating an exemplary fluid-delivery devicebeing secured directly to the skin of the patient.

FIGS. 3 a-c are views illustrating connection of an exemplary fluiddelivery device to a cradle unit.

FIGS. 4 a-c are views illustrating connection and disconnection of anexemplary fluid delivery device from a port unit.

FIGS. 5 a-c are schematic diagrams and views of an exemplary cradleunit.

FIGS. 6 a-c are schematic diagrams and views of an exemplary port unit.

FIGS. 7 a-b are schematic and isometric views of an exemplary disposablepart of a fluid delivery device.

FIGS. 8 a-b are schematic and isometric views of an exemplary reusablepart of a fluid delivery device.

FIG. 9 is a schematic diagram of an exemplary fluid delivery device thatincludes a reusable part and a disposable part.

FIGS. 10 a-b are schematic diagrams of exemplary disposable parts.

FIGS. 11 a-g are schematic diagrams and views depicting an exemplaryreservoir-filling process using a plunger.

FIGS. 12 a-b are schematic diagrams illustrating exemplary connection ofthe therapeutic fluid container to an adapter.

FIGS. 13 a-f are views and diagrams illustrating an exemplaryreservoir-filling process using a syringe.

FIGS. 14 a-c are schematic diagrams of an exemplary cannula cartridgeunit before and after insertion.

FIGS. 15 a-b are schematic diagrams depicting connection of an exemplaryfluid delivery device to an exemplary cradle.

FIG. 16 is a perspective view of an exemplary manually-powered fluiddelivery device with a user-actuated rotation wheel.

FIGS. 17 a-b are schematic diagrams of an exemplary manually-powereddelivery device with a piston-based pumping mechanism.

FIG. 18 is a perspective view of an exemplary delivery device withmanual-power actuation mechanism and a limiter.

FIGS. 19 a-c are schematic diagrams of an exemplary fluid deliverydevice with a piston-based pumping mechanism and a limiter.

FIG. 20 is a schematic diagram of an exemplary manually-powered fluiddelivery device with a peristaltic-based pumping mechanism.

FIGS. 21 a-c are perspective views of an exemplary manually-poweredactuation process using a spring mechanism.

FIG. 22 is a schematic diagram of an exemplary manually-powered fluiddelivery device with a spring mechanism.

FIGS. 23 a-c are perspective views illustrating operation of a pump-airfluid delivery device.

FIGS. 24 a-b are schematic diagrams of a fluid delivery device using apump-air mechanism.

FIGS. 25 a-c are schematic diagrams of another exemplary configurationfor a fluid delivery device with a piston-based mechanism.

FIGS. 26 a-b are perspective views of an exemplary fluid delivery devicewith a detachable counter.

FIGS. 27 a-c are schematic diagrams illustrating connection of anexemplary counter to a fluid delivery device.

FIGS. 28 a-b are schematic diagrams of an exemplary counter implementedwith an optical sensing mechanism.

FIGS. 29 a-c are perspective views of an exemplary fluid delivery devicewith a detachable reservoir.

FIGS. 30 a-b are views of exemplary reservoirs of different sizes.

DETAILED DESCRIPTION OF DRAWINGS

Disclosed are ambulatory therapeutic fluid delivery devices and methods.A disclosed device includes at least one housing connectable to acannula, the at least one housing retaining a reservoir to hold thetherapeutic fluid, a mechanically powered pumping mechanism to causedelivery of at least some of the fluid from the reservoir, and apower-transfer mechanism (i.e., a driving mechanism) to transfermanually-delivered power provided by a user to mechanically actuate thepumping mechanism. The mechanically-powered pumping mechanism isconfigured to operate without using electrically-generated power. Insome embodiments, the power-transfer mechanism includes a user-actuatedrotateable wheel, and one or more gears coupled to the rotateable wheeland further coupled to the mechanically-powered pumping mechanism. Theone or more gears are configured to actuate the pumping mechanism tocause the delivery of the at least some of the fluid in response torotation of the user-actuated wheel. In some embodiments, themechanically-powered pumping mechanism includes a piston coupled to thereservoir and further coupled to the power-transfer mechanism. Actuationof the piston by the power-transfer mechanism causes displacement of thepiston such that the piston causes at least some of the fluid in thereservoir to be displaced. In some embodiments, the pumping mechanismincludes a peristaltic-type pumping mechanism and/or an inflatable aircontainer to actuate the reservoir. Other types of power-transfermechanisms and/or mechanically actuated pumping mechanisms may be used.

In some embodiments, fluid infusion device described herein includes thefollowing units:

-   -   A dispensing patch unit having a reservoir and a driving        mechanism (i.e., power-transfer mechanism). The dispensing patch        unit (hereinafter referred to as the “patch unit” or the        “dispensing device” or the “fluid delivery device”) may include        one or more parts. The dispensing patch unit can be secured        (e.g., adhered) directly to the skin of the patient.    -   A cradle unit that is securable (e.g., adherable) to the skin of        the patient and configured to enable connection and        disconnection of the dispensing patch unit.    -   A cannula cartridge unit that includes a cannula and is        configured to, among other things, shield the sharp end of a        penetrating member which is deployed in the cannula cartridge        unit before and after insertion.

In some embodiments, the device may include a port unit. The port unitmay be configured to enable connection of the dispensing device duringoperation of the device (e.g., delivery of a drug to the body of thepatient). After completion of operation of the device, the dispensingpatch unit may be disconnected from the port unit and kept away from thebody of the patient.

Referring to FIGS. 1 a-6 c, schematic diagrams and views illustrating anexemplary fluid infusion device 10 and various exemplary configurationsto attach the device 10 to the body of the patient are shown. FIG. 1 ais a schematic diagram of an exemplary single-part fluid delivery device10. FIG. 1 b is a schematic diagram of an exemplary two-part fluiddelivery device 10. The two-part device 10 may be configured to includea reusable part 100 and a disposable part 200. The reusable part 100 mayinclude relatively expensive components of the device 10 such as, forexample, a driving mechanism (i.e, a power transfer mechanism) to causefluid delivery from the reservoir to the patient's body. The disposablepart 200 may include the relatively cheaper and replaceable componentsof the device 10 such as, for example, the reservoir, cannula, etc.

Referring to FIGS. 2 a-c, views depicting exemplary ways of securing thedevice 10 to the skin 5 of a patient are shown. FIG. 2 a illustratesremoval of an adhesive protection layer 101 from the dispensing device10. FIG. 2 b illustrates securing the dispensing device 10 to the skin 5of the patient. FIG. 2 c illustrates the device 10 being secured (e.g.,adhered) to the skin 5 of the patient. The device 10 may be adhereddirectly to the skin 5 of the patient.

Referring to FIGS. 3 a-c, views illustrating an exemplary cradle unit 20that is secured to the skin 5 of the patient are shown. The dispensingdevice 10 may be connected to and disconnected from the cradle unit 20at the patient's discretion. FIG. 3 b shows exemplary connection of thedispensing device 10 to the cradle unit 20. FIG. 3 c illustrates anexemplary dispensing device 10 being connected to the cradle unit 20 andready to operate.

Referring to FIGS. 4 a-c, views illustrating an exemplary port unit 30secured to the skin 5 of a patient are shown. The dispensing device 10may be connected to the port unit 30 during operation of the device 10(e.g., during drug delivery). After completion of the drugadministration, the dispensing device 10 may be disconnected from theport unit 30 and kept away from the patient. A description of port unitssimilar to the port unit 30 are provided, for example, in co-owned U.S.Provisional Application No. 60/963,039, filed Aug. 1, 2007, and entitled“Device and Method for the Infusion of Therapeutic Fluid and Sensing ofBodily Analytes,” U.S. Provisional Application No. 61/008,694, filedDec. 21, 2007, and entitled “Device and Method for the Infusion ofTherapeutic Fluid and Sensing of Bodily Analytes,” as well is inco-owned non-provisional U.S. patent application entitled “Device andMethod for the Infusion of Therapeutic Fluid and Sensing of BodilyAnalytes,” filed on the same day as the present application, thecontents of all of which are hereby incorporated by reference in theirentireties. The port unit 30 is configured to enable the patient/user toadhere a much smaller and less bulky item to the skin 5 instead ofsecuring the larger cradle unit 20 to the skin 5. The port unit iscoupleable to a cradle unit and/or a fluid delivery device. In someembodiments, the patient cannot leave the dispensing device 10 attachedto the body when using the port unit 30. FIG. 4 a illustrates the portunit 30 being adhered to the body of the patient FIG. 4 b illustrates anexemplary connection of the dispensing device 10 to the port unit 30.FIG. 4 c illustrates the dispensing device 10 being disconnected fromthe port unit 30.

Referring to FIGS. 5 a-c, schematic diagrams and views of an exemplarycradle unit 20 are shown. FIG. 5 a is a cross-sectional view of thecradle unit 20 secured (e.g., adhered) to the skin 5 of the patient. Thecradle unit 20 includes a flat surface 300 with an adhesive layerattached to its bottom (not shown in FIG. 5 a) and latches 302 and (304)to secure a dispensing device to the cradle unit 20. The cradle unitalso includes a well 310 to enable passage of a cannula (not shown inFIG. 5 a) during its insertion into the skin (e.g., into thesubcutaneous tissue). FIG. 5 b is a top view of the cradle unit 20. FIG.5 c is an isometric view of the cradle unit 20.

Referring to FIGS. 6 a-c, diagrams of an exemplary port unit 30 areshown. FIG. 6 a is a cross-sectional view of the port unit 30 beingsecured (e.g., adhered) to the skin 5 of the patient. FIG. 6 b is a topview of the port unit 30. FIG. 6 c is an isometric view of the port unit30. The port unit 30 includes a flat surface 401 having an adhesivelayer attached to its bottom (not shown in FIGS. 6 a-c) and latches 402,404 and 406 to secure the dispensing device 10 to the port unit 30. Acannula (not shown in FIGS. 6 a-c) may be inserted via the well 310using an inserter such as an inserter described, for example, inco-owned International Patent Application No. PCT/IL08/000,860, filedJun. 25, 2008, claiming priority to U.S. Provisional Patent ApplicationNo. 60/937,214, entitled “Insertion device for inserting a cannula intoa body,” filed on Jun. 25, 2007, the content of which is herebyincorporated by reference in its entirety.

Referring to FIGS. 7 a-9, schematics and views of an exemplary two-partdispensing patch device 10 that includes a disposable part and areusable part are shown.

FIG. 7 a illustrates an exemplary disposable part 200. The disposablepart 200 includes a reservoir 220, a tube 230 and an outlet port 213through which therapeutic fluid (e.g., insulin) can be injected to thebody of the patient. FIG. 7 b is an isometric view of the disposablepart 200. The disposable part 200 can be configured to be replacedeither at predetermined time intervals (e.g., 3 day intervals), wheneverthe reservoir 220 becomes empty, or automatically.

Referring to FIG. 8 a, a schematic diagram of an exemplary reusable part100 of a fluid-dispensing device is shown. The reusable part 100includes a mechanical driving and pumping mechanism (collectivelydesignated 150 in FIG. 8 a), a counter 900 and one or more actuationunits 14 to, for example, transfer manual-power provided by the user topower the driving and/or pumping mechanisms. The driving and pumpingmechanism 150 may be configured as low-cost mechanisms manufactured fromrelatively inexpensive components. FIG. 8 b is an isometric view of thereusable part 100.

Referring to FIG. 9, a schematic diagram of an exemplary assembled twopart dispensing device 10 is shown. Specifically, the device 10 includesa reusable part 100 coupled to a disposable part 200. In someembodiments, the pumping mechanism 150 may be configured to bemechanically coupled to the reservoir 220 (e.g., in implementations thatincludes a piston-type pumping mechanism) or to the delivery tube 230(e.g., in implementation that include a peristaltic-based pumpingmechanism). The disposable part 200 includes a reservoir 220 that may befilled prior to attachment of the disposable part 200 to the reusablepart 100.

Referring to FIGS. 10 a-13 f, diagrams depicting an exemplarypiston-type pumping mechanism and exemplary ways of filling thereservoir 220 with therapeutic fluid are shown.

Referring to FIG. 10 a, a schematic diagram of an exemplary disposablepart 200, functioning by itself as a reservoir 220, is shown. In thisconfiguration, the volume of the reservoir 220 is limited by the volumeof the disposable part 200. The device includes a piston-type pumpingmechanism. The pumping mechanism is provided with a piston 112 whichincludes a plunger rod 110 and a plunger head 111. The piston isconfigured to push fluid towards an outlet port 213 that is typicallysituated at the bottom of the disposable part 200. FIG. 10 b depictsanother implementation of an exemplary disposable part 200 that includesdedicated reservoir 220 and a piston 112. In the shown embodiment ofFIG. 10 b, the piston 112 includes a plunger rod 110 and a plunger head111. The piston 112 can be situated inside the reservoir 220. A tube 230is provided to deliver therapeutic fluid from the reservoir 220 to theoutlet port 213.

Referring to FIG. 11 a, a cross-sectional schematic diagram of anexemplary disposable part 200, similar to the disposable part 200depicted in FIG. 10 b, is shown. The disposable part is depicted priorto filling of the reservoir 220 with fluid. Filling of the reservoir 220is performed using a plunger rod 110 and a plunger head 111. Referringto FIG. 11 b, a diagram of an exemplary drug vial 9 prior to itsconnection to the disposable part 200 is shown. FIG. 11 c illustratesthe vial 9 connected to the outlet port 213. As shown, the disposablepart 200 may include a connecting lumen 250 to pierce the vial septum 7to enable fluid to be drawn from the vial 9 to the reservoir 220 using,for example, a retractable plunger. FIGS. 11 d-11 f illustrate anexemplary filling procedure of the reservoir 220. The amount of fluid tobe drawn may be determined based on the patient's daily dose requirementto thus reduce therapeutic fluid waste. FIG. 11 g illustrates exemplarypriming (e.g., air purging) of the reservoir 220. Air bubbles can bepurged by holding the disposable part 200 in a substantially uprightposition (i.e., when the outlet port 213 is generally elevated) andgently pressing the plunger 112 until fluid 8 is seen to be drippingfrom the outlet port 213.

Referring to FIG. 12 a-b, schematic diagrams of another exemplaryreservoir filling procedure using an auxiliary adapter 216 are shown.FIG. 12 a depicts the adapter 216 having two ports: an upper port 211and a lower port 211′. The upper port 211 is configured to be connectedto the vial 9 and may be provided with a needle 215 to pierce the vial'sseptum 7. The lower port 211′ is configured to be connected to thereservoir 220 and can be sealed with a rubber septum 217 that ispierceable by a lumen 250 disposed in the outlet port 213. Adisplaceable piston 112 may be received (at least partially) within thevolume of the reservoir 220 of the disposable part 200. FIG. 12 billustrates an exemplary connection of the adapter 216 to the disposablepart 200 and the vial 9. To draw fluid from the vial 9, the piston 112is retracted outwardly from the inner volume of the reservoir 220 tocause fluid from the vial to be received.

In some embodiments, the reservoir 220 of the dispensing device may befilled using a syringe. Referring to FIGS. 13 a-f, diagrams depicting anexemplary reservoir-filling procedure using a syringe 80 are shown. FIG.13 a illustrates fluid being drawn from the vial 9. FIG. 13 billustrates the reservoir 220 having an outlet port 213 at its bottomsurface. In some embodiments, the reservoir 220 can be connected to theoutlet port 213 via a tube (not shown in FIG. 13 a). The syringe needle218 is configured to pierce the rubber septum 219 of the inlet port 212to enable filling. Referring to FIGS. 13 c-13 e, diagrams depictinganother exemplary reservoir-filling procedure using a syringe are shown.FIG. 13 f illustrates an exemplary priming procedure of the reservoir220. As shown in FIG. 13 f, the reservoir is filled until fluid drops 8begin to drip from the outlet port 213.

Referring to FIG. 14 a, a schematic diagram of an exemplary cannulacartridge unit 400 is shown. The cannula cartridge unit 400 includes acannula hub 414, a septum 311 and a cannula 6. FIG. 14 b illustrates anexemplary port unit 30 configured to receive the cannula cartridge unit400. The port unit includes a well 310 through which the cannulacartridge unit 400 is inserted. The cannula cartridge unit 400 can beinserted using, for example, an inserter (e.g., manual, semi-automaticand/or automatic). A description of such an exemplary inserter isdisclosed, for example, in co-owned International Patent Application No.PCT/IL08/000,860, filed Jun. 25, 2008, claiming priority to U.S.Provisional Patent Application No. 60/937,214, entitled “Insertiondevice for inserting a cannula into a body,” filed on Jun. 25, 2007, thecontent of which is hereby incorporated by reference in its entirety.FIG. 14 c illustrates cannula cartridge unit 400 that has been insertedinto the well 310 of the port unit 30 and the cannula 6 subcutaneouslyinserted into the patient's skin.

Referring to FIG. 15 a, a schematic diagram of an exemplary fluiddelivery device 10 positioned to being connected to the port unit 30 isshown. FIG. 15 b illustrates the exemplary device 10 connected to theport unit 30. As shown, a connecting lumen 214, provided in the fluiddelivery device, is configured to pierce the septum 311 of the port unitto thus enable fluid to flow from the reservoir 220 to the cannula 6 andto the subcutaneous layer 4.

Referring to FIGS. 16-25 c, diagrams and views illustrating variousexemplary manually-powered driving and pumping mechanisms are shown.

FIG. 16 is a perspective view of an exemplary dispensing device 10. Thedispensing device 10 can be provided with any of the above-describedcomponents/units and/or with a dedicated controller to performmanual/semi-automatic/automatic/or otherwise regulate fluid delivery tothe body of the patient. In some embodiments, such a controller enablesmanual actuation of a driving and/or pumping mechanism of the device 10and may include, for example, an activation wheel 195. As will becomeapparent below, rotation of the activation wheel (also referred to as anactuation wheel) 195 causes fluid infusion/delivery. A counter 900 maybe disposed on the dispensing patch unit to enable control of to bedelivered dose(s). Manual rotation of the activation wheel 195 may causeactuation of the pumping mechanism (e.g., piston-type orperistaltic-type pumping mechanism) to thus cause fluid infusion to beperformed. For an accurate control of fluid delivery, an indicatorproducing a signal (e.g., a click sound, a visual indication such asflashing light, or any other indication) may be provided to accompanyactivation/actuation of the wheel 195. In some embodiments, theactivation wheel rotation is rotatable in a unidirectional manner toprevent retraction of delivered therapeutic fluid back into thereservoir. Alternatively and/or additionally, the pumping mechanism maybe retracted in particular situations, such as, for example, duringreservoir filling, reservoir replacement, to verify the drivingmechanism proper functionality, etc.

Referring to FIG. 17 a, a schematic diagram of an exemplary fluiddelivery device 10 that includes an activation/actuation wheel 195operatively coupled to a piston-type pumping mechanism 151 is shown. Theactivation wheel 195 may be connected to a power-transfer mechanism(also referred to as a driving mechanism) to transfer manually-deliveredpower provided by a user to mechanically actuate a pumping mechanism.The delivery device may thus be implemented without usingelectrically-generated power. The driving mechanism may include, in someembodiments, one or more gears. For example, the one or more gears mayinclude a small-size cog-wheel 606 having teeth that can engage withteeth of a larger cog-wheel 615. Rotation of the wheel 195 causes thelarger cog-wheel 615 to turn and to consequently rotate a worm 610. Oneend of the worm 610 is rigidly connected to one side of a rod 612. Theother side of the rod 612 is connected to a cog-wheel 608. Rotation ofthe cog-wheel 608 urges a screw-nut 614 operatively coupled therewith toturn. By turning the screw-nut 614, the threaded rod of piston 112 ofthe pumping mechanism, which is operatively coupled to the screw-nut, islinearly displaceable in a forward direction. When linearly displaced,the piston 112 is configured to push fluid within the reservoir 220 andforce it to pass through the tube 230 and exit from the outlet port 213.

FIG. 17 b further illustrates the piston-type pumping mechanism duringmovement of the piston 151, which forces fluid to exit through theoutlet port 213. After completing the infusion operation and depletingthe reservoir, the user (e.g., patient) can manually retract the piston112 (e.g., using a handle coupled to the piston 112) backward until thepiston is in its initial position, whereupon the reservoir and/or theentire disposable part 200 may be replaced with a new one.

Referring to FIG. 18, an isometric view of another exemplaryconfiguration of the device 10 implemented using a piston-type mechanismis shown. The dispensing device may be provided with rotatingactivation/actuation wheel 195, a limiter handle 197 and a limiter track199. A counter 900 may be provided to facilitate manual control of thefluid delivery.

Referring to FIG. 19 a, a schematic diagram of another exemplary fluiddelivery device with a manually-powered driving and pumping mechanism,similar to those depicted in FIGS. 17 a-b, and that further includes alimiter 616 is shown. The limiter 616 is configured to preventdisplacement of the piston beyond a pre-set spatial position defined bythe limiter. The pumping mechanism is provided with a screw-nut 613 anda limiter's nut 614. The rotating screw nut 613 rotates the limiter'snut 614 which consequently displaces the limiter 616 in a forwarddirection or by actuating the piston with the driving mechanism. Thelimiter 616 position sets the allowed distance for piston displacement.The displacement of the piston 112 may be performed, for example, bypushing the handle 197 in a forward direction. Piston displacement canbe halted when the piston's bottom end 618 comes in contact with thelimiter 616. In some embodiments, additional safety measures may beemployed to enable the patient to press the handle 197 in a downwarddirection prior to displacement of the handle 197. Such safety measureswould prevent unintentional bolus delivery. FIG. 19 b illustrates anexemplary device 10 after dose adjustment, performed by rotating theactivation/actuation wheel 195 which causes the limiter 616 to advancean to initial position. FIG. 19 c illustrates the piston 112 at the endof the drug delivery operation when the bottom end 618 of the pistonreaches the point of contact with the limiter 616. In some embodiments,the limiter may be actuated separately from the driving mechanism.Alternatively and/or additionally, the limiter may be used as a safetymechanism to lock the driving mechanism and to thus prevent accidentalfluid delivery.

Referring to FIG. 20, a schematic diagram of another exemplaryfluid-delivery device 10, implemented using peristaltic-based mechanism154, is shown. The device 10 includes a rotateable activation/actuationwheel 195 coupled, e.g., via an axle 504, to a small-size gear(cog-wheel) 506. Rotation of the activation wheel 195 causes the twoother larger gears 508 and 510 to rotate to cause rotation of aperistaltic rotor 512.

The peristaltic rotor 512 is configured, during its rotation, to press atube 230 against a stator 530 to enable fluid pumping towards the outletport 213 and into the patient's body. A counter 900 is included with thedevice 10 to count the number of wheel revolutions to thus indicate theamount of drug dose (e.g., insulin units) delivered.

It is to be noted that in the embodiments described above in connectionwith FIGS. 16-20, the fluid dispensing patch unit can be provided withfunctionality for autonomous control of the fluid delivery (e.g.,without implementing automatic control to automatically regulate theextent of pump actuation and/or fluid delivery). This capability can berendered by virtue of providing the dispensing patch unit with adedicated control mechanism operatively coupled to the dispensingmechanism. Autonomous control of fluid delivery can enable manufacturingof a dispensing patch unit 10 without expensive electronics or opticalcomponents. The second advantage of such a patch unit lies in the factthat it removes apprehensions a user may have about using a deviceimplemented using automatic fluid infusion capability (e.g., a devicewhich electronically controls the amount of insulin delivered to his/herbody). Thus, with devices such as the exemplary devices describedherein, the patient manually controls the fluid delivery and is able toactuate (including starting, stopping and/or resuming) drug delivery athis/her own discretion.

Referring to FIGS. 21 a-c, diagrams of an exemplary fluid deliverydevice 10 having a spring-based mechanism to actuate the power-transferand/or pumping mechanism of the device is shown. The spring mechanism isprovided with a spring, loadable upon pulling a spring handle 702connected to a pulling string 704 to enable delivery of a pre-determineddosage (e.g., bolus dosage). This mechanism thus frees the patient/userfrom having to continually manually actuate the device until delivery ofthe required dosage is completed. Thus, after the spring of the springmechanism is loaded (i.e., the string is pulled), the release of thespring (e.g., to cause delivery of bolus dosage) requires no additionaloperational intervention from the patient. FIG. 21 a illustratesdispensing device 10 prior to commencement of delivery operations. FIG.21 b illustrates the device 10 in operation, i.e., during the pullingaction. As shown, the string coupled to the spring is pulled, using apulling-spring handle 702 to an initial position. Particularly, thestring coupled to the spring is pulled in a rotational directionopposite the rotational direction at which the spiral spring is biased.FIG. 21 c illustrates retraction of the pulling string 704 upon releaseof the pulling handle 702. Release of the string causes the spiralspring to rotate in the direction in which the spiral spring is biasedto thus cause rotation of the at least one gear coupled to thespring-based mechanism.

Referring to FIG. 22, a schematic diagram of a driving mechanism(power-transfer mechanism) 152 actuated by a spiral spring 706 (in amanner similar to that shown in relation to FIGS. 21 a-c) is shown. Ahandle 702 is connected to the spiral spring 706 by a string 704. Bypulling the handle 702, the patient loads the spiral spring 706. Uponrelease of the handle 702, the spiral spring 706 is discharged anddrives one or more gears, for example, the cogwheels 714, 716 and 718.The one or more gears of the driving mechanism cause, in turn, a rotor512 of the peristaltic-based mechanism to be rotated. Rotation of therotor 512 causes dispensation of fluid via the tube 230 to the outletport 213 and to the body of the patient. Each string pulling andreleasing action corresponds to the discharge of a predetermined dose(e.g., 1 IU of insulin) into the body of the patient. In someembodiments, this driving mechanism 152 can be employed to actuate apiston-type pumping mechanism (not shown in FIG. 22). The drivingmechanism 152 may be configured to impart to the dispensing patch unitan ability for autonomous control of fluid delivery, i.e. the dispensingis completely controlled by the patient (e.g., the user providesentirely the actuation required to cause operation of the drivingmechanism and/or the pumping mechanism).

Referring to FIGS. 23 a-c, perspective views of an exemplary fluiddelivery device including a user-actuated “pump-air” infusion pump isshown. FIG. 23 a illustrates fluid pumping by pressing buttons 15provided on both sides of the device 10. FIG. 23 b illustrates pumpingby pressing a pumping button 16 situated on the top of the device 10.FIG. 23 c illustrates pumping by using activation/actuation mechanismconfigured as a blower 17. A transparent window 950 enables monitoringof the content of reservoir 220.

Referring to FIGS. 24 a-b, schematic diagrams of an exemplary fluiddelivery device 10 that includes a “pump-air”-based mechanism 153 isshown. The pump-air mechanism includes an inflatable air container 802to actuate the reservoir 220, and at least one air-injection device todeliver air to the inflatable air container. In some embodiments, eachof the at least one air injection device includes an air tube incommunication with the air container and an air compression chamber incommunication with the air tube. The air compression chamber includes aplunger displaceable by the user within an inner volume of the aircompression chamber. In some embodiments, the plunger is implemented asa user-actuatable button 15 coupled to an outwardly biased spring.Actuation of the button to push it inwards into the air compressionchamber causes air to be pumped into the air container. When the userreleases the button, the outwardly biased spring causes the button to bedisplaced outwardly to its initial position to thus cause ingress ofambient air into the air compression chambers 808. FIG. 24 a illustratesa dispensing device 10 in its initial state prior to operation, at whichpoint the buttons 15 are not pressed and the displaceable plungers(e.g., the buttons coupled to the springs 806) are in their releasedpositions. As shown, the inflatable air container 802 is connected viaair tubes 810 and unidirectional valves 803 to the air compressionchambers 808. In the schematic of FIG. 24 a, the air container issubstantially empty. FIG. 24 b illustrates the device 10 in operation.By pressing the buttons 15, air is pushed from the chambers 808 via theair tubes 810 and the unidirectional valves 803 into the air container802. The air container 802 inflates and causes actuation of thereservoir 220 to thus cause dispensation of the fluid from the reservoir220. The air container 802 remains inflated as the air movement out islimited by the unidirectional valves 803. In some embodiments, airmovement into the air compression chambers is directed by unidirectionalvalves enabling entrance of ambient air into the chamber and preventingits release from the air compression chambers.

Referring to FIG. 25 a, a schematic diagram of an exemplary device 10prior to its connection to an indicator (counter) 900 is shown. As shownin FIG. 25 a, racks of the rod 58 and racks of the gear 56 are notengaged at that point. Thus, rotating the gear 56 will not move theplunger 55. FIG. 25 b illustrates an exemplary device 10 afterconnection of the counter 900. The connection of the counter 900 to itshousing 907 engages the gear 56 and the threaded rod 58. FIG. 25 cillustrates the device 10 in operation. By turning the rotation wheel50, a set of gears (cog wheels) are actuated. The teeth of the gear 56and the thread of the threaded rod 58 are configured to engage and causethe plunger 55 to move in a forward direction, which causes infusion tooccur.

Referring to FIGS. 26 a-b, perspective views of an exemplary detachabledigital counter 900 to facilitate reservoir content monitoring andcontrol is shown. Detaching the counter 900 enables the patient toestimate the status of the dispensing device 10 without suspending itsoperation. FIG. 26 a illustrates the digital counter 900 being detachedfrom its housing 907. The counter 900 can be detached by, for example,pressing a release button 903. FIG. 26 b illustrates the counter clock900 being grasped by the patient (e.g., held in the patient's hand). Thepatient can connect and/or disconnect the digital counter 900 while thepump 10 remains attached to the body and in continued operation. Thecounter 900 may be a mechanical, electrical, optical or electrochemicalcounter. In some embodiments, the counter and the dispensing device maycommunicate wirelessly, enabling status update of the dispensing devicewhen the counter is detached from the device.

Referring to FIGS. 27 a-28 b, schematic diagrams of exemplary durableoptical counter 900 are shown.

FIG. 27 a is a schematic diagram of an exemplary embodiment of a counter900. The counter 900 includes of a power source (e.g., a battery 62),and two connectors 65 and 65′, a counting controller 64 to perform thecounting operations and a display 66. FIG. 27 b is a schematic diagramof an exemplary fluid delivery device 10 (e.g., a device implementedusing a peristaltic-based pumping mechanism) without the counter 900being connected to the device. The reusable part 100 of the device 10includes a measurement unit to determine the extent of fluid delivery.Such a measurement unit may include an optical sensing unit 70 and twoconnectors 67 and 67′. The optical sensing unit 70 is configured todetect one or more markings disposed on the power-transfer mechanism(the driving mechanism). Detection of the one or more marking isindicative that a pre-determined amount of therapeutic fluid wasdelivered. The optical sensing unit includes a source of light and adetector. The source of light and the detector can be configured to belocated on each side of one of the gears constituting the drivingmechanism (e.g., the cog wheel 69). In some embodiments, the markings onthe cog wheel 69 may be holes 73 and 73′. FIG. 27 c depicts the counter900 being connected to the device 10. By connecting the counter 900 tothe device 10, the device's electrical circuit is closed and therebyenables measurement of data by the optical sensor 70, wherein such datais forwarded to the counter 900 and displayed. Specifically, the lightsource of the optical unit 70 is configured to illuminate a light beamtowards one surface of the cog wheel 69. As the cog wheel rotates, theposition of at least one of the holes will cross the path of theilluminated light beam, and as a result the light beam will pass throughthe hole and be detected by the sensor. Detection of the light beam willthus indicate that a particular amount of fluid (corresponding to theamount of fluid resulting from rotation of the cog wheel 69 by a certainamount) has been delivered.

FIG. 28 a illustrates light 2000 passing through one of the holes 73′ inthe cog-wheel 69 from the light source 71 to the optical detector 72.FIG. 28 b illustrates light 2000 being blocked when it cannot passthrough the cog wheel 69 (thus indicating that the pre-determined amountof fluid has not yet been fully delivered).

FIGS. 29 a-c illustrate exemplary ejection of a replaceable reservoir.Patients of Type 2 DM pumps use reservoirs with different reservoirvolumes (e.g., different amount of insulin) depending on various medicaland body conditions/needs. Replacing only the reservoir within thedispensing device 10 enables the patient to use the same dispensingpatch unit 10 and change the amount of fluid to be delivered withoutreplacing the whole patch unit 10. FIG. 29 a illustrates an exemplaryreservoir cover 222 opened by pressing a button 224. FIG. 29 billustrates the reservoir 220 inside its chamber 226 while the chambercover 222 is open. FIG. 29 c illustrates ejection of the reservoir 220from the chamber 226.

FIG. 30 a-b illustrate exemplary various-size reservoirs 220 that may beemployed in the dispensing device 10. Particularly, FIG. 30 a shows a 2IU size insulin reservoir 220, while FIG. 30 b shows a 5 IU insulinreservoir 220.

Although particular embodiments have been disclosed herein in detail,this has been done by way of example for purposes of illustration only,and is not intended to be limiting with respect to the scope of theappended claims, which follow. In particular, it is contemplated thatvarious substitutions, alterations, and modifications may be madewithout departing from the spirit and scope of the invention as definedby the claims. Other aspects, advantages, and modifications areconsidered to be within the scope of the following claims. The claimspresented are representative of the inventions disclosed herein. Other,unclaimed inventions are also contemplated.

1.-69. (canceled)
 70. A portable ambulatory therapeutic fluid deliverydevice for delivering a therapeutic fluid in bolus doses into a body ofa patient, the device comprising: at least one housing connectable to acannula, and a cradle securable to the patient's skin, wherein thecradle is configured for releasably receiving the at least one housingenabling connection and disconnection of the at least one housingtherefrom; the at least one housing including: a reservoir for storing atherapeutic fluid; a pump for delivering one or more bolus doses of thetherapeutic fluid from the reservoir to the body of the patient throughthe cannula, wherein the pump is configured for non-electricaloperation; and an actuator for transferring manual power provided by thepatient for operating the pump; wherein displacement of the pump islimited for delivery of a bolus dose corresponding to a pre-determinedamount.
 71. The device of claim 70, wherein the therapeutic fluidincludes one or more of: insulin, pramlintide acetate and exenatide. 72.The device of claims 70 wherein the at least one housing includes: adisposable part housing including at least a part of the reservoir andan outlet port for enabling passage of the fluid to the body of thepatient; and a reusable part housing removably attachable to thedisposable part, the reusable part housing including at least a portionof the pump and the actuator; wherein the device is operable uponattachment of the reusable part housing and the disposable part housing.73. The device of claim 70, wherein the actuator comprises auser-actuated rotatable wheel and one or more gears for transferringpower between the wheel and the pump for causing delivery of a bolusdose in response to rotation of the user-actuated wheel.
 74. The deviceof claim 73, wherein the one or more gears comprise at least one cogwheel in mechanical communication with at least one worm gear and ascrew-nut coupled to the worm gear and further coupled to a piston ofthe pump such that rotation of the worm gear causes displacement of thepiston.
 75. The device of claim 70, wherein the pump comprises: a pistoncoupled to the reservoir, the piston further coupled to the actuator;wherein movement of the piston by the actuator results in displacementof the piston for delivery of a bolus dose.
 76. The device of claim 70,further comprising a limiter for limiting displacement of the pump,wherein the limiter prevents displacement of the pump or the actuatorbeyond a pre-set spatial position defined by the limiter correspondingto a bolus dose.
 77. The device of claim 76, wherein the predeterminedamount of a bolus dose is configurable by user adjustment of thelimiter.
 78. The device of claim 76, wherein the limiter comprises astationary block for engaging a projection extending from an end of thepiston such that upon contact between the stationary block and theprojection extending from the end of the piston, further displacement ofthe piston is prevented.
 79. The device of claim 70, wherein the pumpcomprises a peristaltic pump, wherein the peristaltic pump comprises arotor coupled to a delivery tube for delivering one or more bolus doses,the rotor further coupled to the actuator such that manual powertransferred by the actuator causes rotation of the rotor resulting indisplacement of therapeutic fluid contained within the delivery tube.80. The device of claim 70, wherein the actuator includes a spiralspring configured to operate the pump upon activation of the spring bythe patient, and wherein the actuator further comprises: at least onegear coupled to the spiral spring, wherein the spiral spring is biasedin a first rotational direction; and a string coupled to the spiralspring for causing rotation of the spiral spring in a second rotationaldirection for increasing in the tension of the spiral spring, whereinupon release of the string, the spiral spring rotates in the firstrotational direction resulting in movement of the actuator resulting inpump operation.
 81. The device of claim 80, further comprising a limiterfor limiting displacement of the pump, wherein the limiter prevents thestring from moving beyond a predetermined position such that uponrelease of the string, the spiral spring rotates a pre-determined radialdistance causing delivery of a bolus dose by the pump corresponding withthe predetermined amount.
 82. The device of claim 70, wherein the pumpcomprises an inflatable air container configured for driving fluid fromthe reservoir, and wherein the actuator comprises at least one airinjection device for delivering air to the inflatable air container. 83.The device of claim 82, wherein the at least one air injection devicecomprises: an air tube in communication with the inflatable aircontainer; and an air compression chamber in communication with the airtube, the air compression chamber including a displaceable plunger,wherein upon movement of the plunger by the patient, air is displacedfrom the air compression chamber into the inflatable air containerthrough the air tube.
 84. The device of claim 70, further comprising anindicator for indicating operation of the pump.
 85. The device of claim84, wherein the indicator includes one or more of: an audible indicatorfor producing a sound and a visual indicator for producing a visualsignal.
 86. The device of claim 70, further comprising a counter fordisplaying a value representative of an amount of therapeutic fluiddelivered by operation of the device.
 87. The device of claim 86,wherein operation of the counter is based on operation of the actuator.88. The device of claim 86, wherein the counter comprises a mechanicallydetachable counter housing configured for attaching and detaching fromthe at least one housing.
 89. The device of claim 70, further comprisinga measurement unit for determining an extent of fluid delivered.
 90. Thedevice of claim 89, wherein the measurement unit comprises an opticalunit for detecting one or more markings disposed on the actuator,wherein detection of the one or more markings corresponds to apre-determined amount of fluid delivered.
 91. The device of claim 90,wherein the actuator comprises a gear having one or more openingsextending from one surface of the gear to the other surface, and whereinthe optical unit comprises: a light source for producing a light beam toilluminate one surface of the gear; and a light sensor for detectinglight passing through the one or more openings.
 92. The device of claim70, wherein the at least one housing is configured for receivingdifferent size reservoirs.
 93. A portable ambulatory therapeutic fluiddelivery device for delivering a therapeutic fluid as bolus doses into abody of a patient, the device comprising: at least one housingconnectable to a cannula; and a cradle securable to the patient's skin,wherein the cradle is configured for releasably receiving the at leastone housing for connection and disconnection of the at least one housingtherefrom; the at least one housing including: a reservoir for storing atherapeutic fluid; a pump for delivering one or more bolus doses oftherapeutic fluid from the reservoir to the body of the patient throughthe cannula, the pump configured for non-electric operation; and auser-actuated rotatable wheel; and one or more gears for transferringforce between the rotatable wheel and the pump, wherein the one or moregears are configured for operating the pump resulting in delivery of oneor more bolus doses in response to rotation of the user-actuated wheel,wherein displacement of the pump is limited for delivery of a bolus dosecorresponding to a pre-determined amount.
 94. A portable ambulatorytherapeutic fluid delivery device for delivering a therapeutic fluid inbolus doses into a body of a patient, the device comprising: at leastone housing connectable to a cannula; and a cradle securable to thepatient's skin, wherein the cradle is configured for releasablyreceiving the at least one housing enabling connection and disconnectionof the at least one housing therefrom; the at least one housingincluding: a reservoir for storing a therapeutic fluid; a pump fordelivery of one or more bolus doses of therapeutic fluid from thereservoir to the body of the patient through the cannula, the pump beingconfigured for non-electrical operation; and an actuator fortransferring manual power provided by the patient for operating thepump, wherein the actuator includes a spiral spring configured formoving the actuator upon release of the spiral spring by the patient,wherein the actuator further comprises: at least one gear coupled to thespiral spring, wherein the spiral spring is biased in a first rotationaldirection; and a string coupled to the spiral spring for causingrotation of the spiral spring in a second rotational direction forincreasing tension of the spiral spring, wherein upon release of thestring, the spiral spring rotates in the first rotational direction forcausing rotation of the at least one gear coupled to the spiral spring,wherein displacement of the pump is limited for delivery of a bolus dosecorresponding to a pre-determined amount.
 95. A portable ambulatorytherapeutic fluid delivery device for delivering a therapeutic fluid inbolus doses into a body of a patient, the device comprising: at leastone housing connectable to a cannula, and a cradle securable to thepatient's skin, the cradle is configured for releasably receiving the atleast one housing enabling connection and disconnection of the at leastone housing therefrom; the at least one housing including: a reservoirfor storing a therapeutic fluid; a pump for delivering one or more bolusdoses of the therapeutic fluid from the reservoir to the body of thepatient through the cannula, wherein the pump is configured fornon-electric operation; an actuator for transferring manual powerprovided by the patient for operating the pump; an inflatable aircontainer for causing displacement of the therapeutic fluid from thereservoir; and at least one manually-actuated air injection device fordelivering air to the inflatable air container, wherein displacement ofthe pump is limited for delivery of a bolus dose corresponding to apre-determined amount.